Journal article

Publication year: 2011

Pages: 344-352

Journal: Cardiovascular Research

Volume number: 89

Issue number: 2

ISSN: 0008-6363

eISSN: 1755-3245

DOI Link: https://doi.org/10.1093/cvr/cvq313

Publisher: Oxford University Press

Abstract: 

Aims Renin and peroxisome proliferator-activated receptor (PPAR-gamma) interact directly with cardiomyocytes and influence protein synthesis. We investigated their effects and interaction on the size of cardiomyocytes.

Methods and results Effects of renin and PPAR-gamma activation were studied in cultured adult rat ventricular cardiomyocytes, transgenic mice with a cardiomyocyte-restricted knockout of PPAR-gamma, and transgenic rats overexpressing renin, TGR(mRen2)27. The length and width of cardiomyocytes were analysed 24 h after administration of factors. Renin caused an unexpected effect on the length of cardiomyocytes that was inhibited by mannose-6-phosphate and monensin, but not by administration of glucose-6-phosphate. Endothelin-1 used as a classical pro-hypertrophic agonist increased cell width but not cell length. Renin caused an activation of p38 and p42/44 mitogen-activated protein (MAP) kinases. The latter activation was impaired by mannose-6-phosphate. Inhibition of p42/44 but not of p38 MAP kinase activation attenuated the effect of renin on cell length. In contrast, activation of PPAR-gamma reduced cell length. Feeding wild-type mice with pioglitazone, a PPAR-gamma agonist, reduced cell length. Cardiomyocytes isolated from PPAR-gamma knockout mice were longer, and their length was not affected by pioglitazone. Cardiomyocytes isolated from TGR(mRen2) 27 rats were longer than those of non-transgenic littermates. Cell length was reduced by feeding these mice with pioglitazone. Pioglitazone affected cell length independent of blood pressure.

Conclusion The length of cardiomyocytes is controlled by the activation of cardiac-specific mannose-6-phosphate/insulin-like growth factor II receptors and activation of PPAR-gamma. This type of cell size modification differs from that of any other known pro-hypertrophic agonists.

Harvard Citation style: Hinrichs, S., Heger, J., Schreckenberg, R., Wenzel, S., Euler, G., Arens, C., et al. (2011) Controlling cardiomyocyte length: the role of renin and PPAR-γ, Cardiovascular Research, 89(2), pp. 344-352. https://doi.org/10.1093/cvr/cvq313

APA Citation style: Hinrichs, S., Heger, J., Schreckenberg, R., Wenzel, S., Euler, G., Arens, C., Bader, M., Rosenkranz, S., Caglayan, E., & Schlueter, K. (2011). Controlling cardiomyocyte length: the role of renin and PPAR-γ. Cardiovascular Research. 89(2), 344-352. https://doi.org/10.1093/cvr/cvq313